This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a Phase-III double blinded placebo controlled trial for Lorenzo's oil treatment in 120 men with pure Adrenomyeloneuropathy and 120 symptomatic female carriers with a similar syndrome. The trial follow-up duration is for 3 years in each patient. The main aim of the trial is to test the efficacy of the Lorenzo's Oil treatment in slowing disability progression in pure Adrenomyeloneuropathy (AMN) patients. Pure AMN and symptomatic female carriers represent the phenotypes of X-ALD, characterized by progressive non-inflammatory axonopathy in the long tracts of the spinal cord. Due to the non-inflammatory nature of the disease progression, visual appreciation of the spinal cord pathology using conventional imaging modalities was until recently a significant challenge. The collaboration with the resource allowed development of magnetization transfer (MT) imaging that provides high spatial resolution and sufficient SNR to distinguish gray and white matter contrast in the cervical spinal cord, allowing visualization of the dorsal column between C1 to C5 of the spinal cord at a field of 1.5 Tesla. This enabled first in vivo evaluation of the spinal cord tracts in pure AMN patients. There were significant quantitative MT differences between men with Pure AMN, symptomatic female carriers and age-matched controls. The abnormality in dorsal column correlated significantly with the dorsal column function tested by quantitatively measuring great toe vibration sensitivity threshold. Based on the initial results of our collaboration with the resource, the current trial employs quantitative modified MT evaluation of the cervical cord as a secondary outcome measure and as a tool for monitoring progression and rapidly evaluating therapy. There is no definitive treatment for neurological aspects of X-ALD. Development of sensitive quantitative biomarker is crucial for rapid evaluation of newer therapeutic agents. Current mainstay of disease evaluation is employing clinical rating scales such EDSS (Expanded Disability Status Scale), modified Rankin scale, Adult adrenoleukodystrophy scale etc. These are relatively less sensitive and require a large sample size and long follow-up to achieve adequate power for detecting significant differences in progression. To circumvent the difficulties associated with conventional clinical markers of progression, there is great emphasis on development of neuroimaging surrogates that are sensitive to ultrastructural abnormalities, specific to axonal and myelin pathology and can be reliably quantified longitudinally, for which the collaboration with the resource is essential. In collaboration with the resource, we hope to expand our neuroimaging endpoints to employ the better sensitivity of higher field as well as include diffusion tensor imaging (DTI) quantification, fiber tracking for the columns, and NAA and Cho measures for larger sections (due to the lower resolution of spectroscopy) of the cord.